Current research describes a new method to track the development of autoimmune diseases
before the onset of symptoms. The related report by Zangani et al, "Tracking early
autoimmune disease by bioluminescent imaging of NF-?B activation reveals pathology in
multiple organ systems," appears in the April 2009 issue of The American Journal of
Pathology. Autoimmune diseases such as lupus, multiple sclerosis, rheumatoid arthritis and
diabetes are caused when the immune system attacks the body's own cells. Normally, immune
cells are prevented from attacking normal cells; however, in patients with autoimmune
disease, this "tolerance" is lost. The immediate causes of autoimmune diseases
remain unknown, partially due to the inability to detect disease before the onset of
symptoms. Early detection of autoimmune disease is critical for assessing new treatments.
The molecule NF-?B is activated by inflammation, which plays a key role in autoimmune
disease development, making NF-?B a prime candidate to track autoimmune activity.
Researchers at the University of Oslo led by Drs. Ludvig Munthe and Bjarne Bogen in
collaboration with Rune Blomhoff engineered NF-?B such that it would emit light when
activated. Using a mouse model of systemic autoimmunity with features of lupus, they found
that NF-?B activation signals were present in affected organs several weeks before the
clinical manifestations of disease. The light signal intensity correlated with disease
progression. NF-?B tracking may therefore provide a new tool in the evaluation of early
autoimmune therapies.

St. Jude researchers have discovered an intriguing insight into how T cells, the immune
systems master regulatory cells, wage war on the bodys own tissues in such
autoimmune disorders as multiple sclerosis, type 1 diabetes and rheumatoid arthritis.
Their findings about T cells add another piece to the puzzle of understanding such
diseases. While the findings are quite basic, they could contribute to designing therapies
to suppress the immune responses that are misdirected against a persons own tissues
in autoimmune disorders.T cells launch the immune system into action when they encounter
bits of foreign protein, called antigens. T cells sense these antigenswhich may come
from invading viruses or bacteriathrough receptors on the T cells surface.
These receptors recognize and attach to specific antigens like a key fitting a lock. Many
autoimmune diseases arise when T cell receptors that recognize the bodys own
proteins, called self antigens, spur T cells to mistakenly launch an immune
system to attack body tissues.T cells have potentially millions of different
possible receptors, said Terrence Geiger, MD, PhD, Pathology, the senior author of a
report on this work that appears in the July 1 issue of the Journal of Immunology.
Some T cell receptors are adept at promoting autoimmunity, some are poor and some
are protective. It is not clear why one T cell receptor can promote autoimmunity, whereas
another T cell receptor on a similar kind of T cell either doesnt do anything, or
even protects against autoimmune reaction.

Distributed around the body, dendritic cells act as the security alarms of the immune
system. After sensing the presence of intruders, dendritic cells can transmit the alarm to
white blood cells or tell them to relax, depending on the signals they send out.
Researchers at the Emory Vaccine Center and Yerkes National Primate Research Center have
discovered that dendritic cells can respond to the same compound, through two different
receptors, by sending out both stimulatory and calming messages at once. The compound is
zymosan, a component of yeast cell walls. However, the finding could guide scientists in
designing vaccines against many infectious agents since the calming receptor is known to
respond to bacteria and viruses as well as yeast. In addition, silencing the calming
receptor's messages might boost the immune system's ability to fight a chronic infection.
The calming receptor, known as TLR2 (Toll-like receptor 2), uses vitamin A to transmit its
signals, which provides an explanation for the connection between vitamin A deficiency and
autoimmune diseases. Vitamin A deficiency has been linked to diseases such as rheumatoid
arthritis, lupus and type I diabetes. This "two signals at once" feature of the
immune system can be viewed as the result of an evolutionary tug of war, says senior
author Bali Pulendran, PhD, professor of pathology and laboratory medicine at Emory
University School of Medicine and Yerkes National Primate Research Center. "The
immune system has to provide a defense against infection, while avoiding the destruction
of too much of the body along the way," he says. "At the same time, pathogens
have evolved strategies to manipulate the immune system for their own purposes."

A potentially blinding neurological disorder, often confused with multiple sclerosis (MS),
has now become a little less mysterious. A new study by researchers at the Mayo Clinic in
Rochester, Minnesota, may have uncovered the cause of Devic's disease. Their new study,
which will appear online on October 6th in the Journal of Experimental Medicine, could
result in new treatment options for this devastating disease. Devic's disease, also known
as neuromyelitis optica (NMO), results in MS-like demyelinating lesions along the optic
nerves and spine. Affected individuals often experience rapid visual loss, paralysis, and
loss of leg, bladder, and bowel sensation. Some lose their sight permanently. Unlike MS,
Devic's disease can be diagnosed by the presence of a specific self-attacking immune
proteinan autoantibody referred to as NMO-IgGin the blood. Until now, however,
clinicians didn't know how that protein damaged nerves and contributed to disease
symptoms. The Mayo team, lead by Dr. Vanda Lennon, now show that NMO-IgG sets off a chain
of events that leads to a toxic build-up of a neurotransmitter called glutamate. NMO-IgG
binds to a protein that normally sops up excess glutamate from the space between brain
cells. When NMO-IgG is around, this sponge-like action is blocked, allowing glutamate to
accumulate. And too much glutamate can kill the cells that produce myelinthe protein
that coats and protects neurons. The authors suggest that glutamate-induced damage to
nerve cells and their insulating myelin coats might account for the neurological symptoms
associated with Devic's disease. If the groups' resultsgenerated using nerve cell
culturesare confirmed in vivo, drug development could be very straightforward.
Therapeutic trials for glutamate blockers, created to treat other neurodegenerative
diseases like Lou Gehrig's disease (or ALS), are already underway.

Deficiency in vitamin D has been widely regarded as contributing to autoimmune disease,
but a review appearing in Autoimmunity Reviews explains that low levels of vitamin D in
patients with autoimmune disease may be a result rather than a cause of disease and that
supplementing with vitamin D may actually exacerbate autoimmune disease. Authored by a
team of researchers at the California-based non-profit Autoimmunity Research Foundation,
the paper goes on to point out that molecular biologists have long known that the form of
vitamin D derived from food and supplements, 25-hydroxyvitamin D (25-D), is a secosteroid
rather than a vitamin. Like corticosteroid medications, vitamin D may provide short-term
relief by lowering inflammation but may exacerbate disease symptoms over the long-term.
The insights are based on molecular research showing that 25-D inactivates rather than
activates its native receptor - the Vitamin D nuclear receptor or VDR. Once associated
solely with calcium metabolism, the VDR is now known to transcribe at least 913 genes and
largely control the innate immune response by expressing the bulk of the body's
antimicrobial peptides, natural antimicrobials that target bacteria. Written under the
guidance of professor Trevor Marshall of Murdoch University, Western Australia, the paper
contends that 25-D's actions must be considered in light of recent research on the Human
Microbiome. Such research shows that bacteria are far more pervasive than previously
thought  90% of cells in the body are estimated to be non-human  increasing
the likelihood that autoimmune diseases are caused by persistent pathogens, many of which
have yet to be named or have their DNA characterized. Marshall and team explain that by
deactivating the VDR and subsequently the immune response, 25-D lowers the inflammation
caused by many of these bacteria but allows them to spread more easily in the long-run.
They outline how long-term harm caused by high levels of 25-D has been missed because the
bacteria implicated in autoimmune disease grow very slowly. For example, a higher
incidence in brain lesions, allergies, and atopy in response to vitamin D supplementation
have been noted only after decades of supplementation with the secosteroid. Furthermore,
low levels of 25-D are frequently noted in patients with autoimmune disease, leading to a
current consensus that a deficiency of the secosteroid may contribute to the autoimmune
disease process. However, Marshall and team explain that these low levels of 25-D are a
result, rather than a cause, of the disease process. Indeed, Marshall's research shows
that in autoimmune disease, 25-D levels are naturally down-regulated in response to VDR
dysregulation by chronic pathogens. Under such circumstances, supplementation with extra
vitamin D is not only counterproductive but harmful, as it slows the ability of the immune
system to deal with such bacteria. The team points out the importance of examining
alternate models of vitamin D metabolism. "Vitamin D is currently being recommended
at historically unprecedented doses," states Amy Proal, one of the paper's
co-authors. "Yet at the same time, the rate of nearly every autoimmune disease
continues to escalate."

Autoinflammatory disease model
reveals role for innate, not adaptive, immunity

Researchers at the University of California, San Diego School of Medicine have developed
the first mouse model for auto-inflammatory diseases, disorders that involve the
over-activation of the body's innate, primitive immune system. Their study, published
early on-line in Cell Immunity on June 4, suggests that the innate  not adaptive
 immune system drives auto-inflammatory diseases. The findings could open new
therapeutic directions for research into disorders such as gout or inflammatory bowel
disease. "Auto-inflammatory diseases are a relatively new classification of diseases
that are different from autoimmune diseases or allergies," said Hal Hoffman, MD,
associate professor of medicine at UC San Diego School of Medicine. Hoffman studies a
group of rare, inherited auto-inflammatory conditions called Cryopyrin-Associated Periodic
Syndromes (CAPS), which includes Familial Cold Auto-inflammatory Syndrome (FCAS) and
Muckle-Wells Syndrome (MWS). Autoimmune diseases arise from an overactive response of the
body's adaptive, or acquired, immune system against substances and tissues normally
present in the body. Allergies are also a product of the adaptive immune system, but in
response to environmental substances. Both involve the action of lymphocytes such as B
cells and T cells. The older innate immune system, on the other hand, recruits immune
cells to sites of infection and inflammation, but doesn't confer long-time protection.
Pathogens evoke an inappropriate response that doesn't involve antibodies or lymphocytes.
With CAPS, Hoffman had earlier discovered that mutations of the NLRP3 gene caused the
auto-inflammatory disease symptoms because the gene causes alterations in the protein
called cryopyrin. Cryopyrin regulates the release of interleukin-1, an important mediator
of fever and systemic inflammation during the body's innate immune response, and
alterations in cryopyrin lead to over-production of Il-1. Mutations in the NLRP3 gene are
thought to result in inappropriate activation of a multi-protein complex called an
inflammasome, leading to excessive Il-1? release and manifestation of CAPS disease
symptoms. Treatment with Il-1? inhibitors reduces the inflammation and symptoms in
auto-inflammatory diseases; however, NLRP3 may have other effects in addition to increased
Il-1?. "Patients treated with the Il-1? inhibitors got much better, but still
exhibited some symptoms," said Hoffman.

A drug derived from the hydrangea root, used for centuries in traditional Chinese
medicine, shows promise in treating autoimmune disorders, report researchers from the
Program in Cellular and Molecular Medicine and the Immune Disease Institute at Children's
Hospital Boston (PCMM/IDI), along with the Harvard School of Dental Medicine. In the June
5 edition of Science, they show that a small-molecule compound known as halofuginone
inhibits the development of Th17 cells, immune cells recently recognized as important
players in autoimmune disease, without altering other kinds of T cells involved in normal
immune function. They further demonstrate that halofuginone reduces disease pathology in a
mouse model of autoimmunity. Currently there is no good treatment for autoimmune
disorders; the challenge has been suppressing inflammatory attacks by the immune system on
body tissues without generally suppressing immune function (thereby increasing risk of
infections). The main treatment is antibodies that neutralize cytokines, chemical
messengers produced by T cells that regulate immune function and inflammatory responses.
However, antibodies are expensive, must be given intravenously and don't address the root
cause of disease, simply sopping up cytokines rather than stopping their production;
patients must therefore receive frequent intravenous infusions to keep inflammation in
check. Powerful immune-suppressing drugs are sometimes used as a last resort, but patients
are left at risk for life-threatening infections and other serious side effects. Through a
series of experiments, the researchers show that halofuginone prevents the development of
Th17 cells in both mice and humans, halts the disease process they trigger, and is
selective in its effects. It also has the potential to be taken orally. "This is
really the first description of a small molecule that interferes with autoimmune pathology
but is not a general immune suppressant," says Mark Sundrud, PhD, of the PCMM/IDI,
the study's first author.

Current research describes a new method to track the development of autoimmune diseases
before the onset of symptoms. The related report by Zangani et al, Tracking early
autoimmune disease by bioluminescent imaging of NF-?B activation reveals pathology in
multiple organ systems, appears in the April 2009 issue of The American Journal of
Pathology. Autoimmune diseases such as lupus, multiple sclerosis, rheumatoid arthritis and
diabetes are caused when the immune system attacks the bodys own cells. Normally,
immune cells are prevented from attacking normal cells; however, in patients with
autoimmune disease, this tolerance is lost. The immediate causes of autoimmune
diseases remain unknown, partially due to the inability to detect disease before the onset
of symptoms. Early detection of autoimmune disease is critical for assessing new
treatments.

Autoimmune diseases have long been regarded as illnesses in which the immune system
creates autoantibodies to attack the body itself. But, researchers at the California
non-profit Autoimmunity Research Foundation (ARF) explain that the antibodies observed in
autoimmune disease actually result from alteration of human genes and gene products by
hidden bacteria. Not long ago, scientists believed they had located all bacteria capable
of causing human disease, But DNA discoveries in the last decade have led the NIH Human
Microbiome Project to now estimate that as many as 90% of cells in the body are bacterial
in origin. Many of these bacteria, which have yet to be named and characterized, have been
implicated in the progression of autoimmune disease. In a paper published in Autoimmunity
Reviews, the ARF team, under the guidance of Professor Trevor Marshall of Murdoch
University, Western Australia, has explained how Homo sapiens must now be viewed as a
superorganism in which a plethora of bacterial genomes  a metagenome  work in
concert with our own. Marshall and team contend that the human genome can no longer be
studied in isolation. "When analyzing a genetic pathway, we must study how bacterial
and human genes interact, in order to fully understand any process related to the human
superorganism," states Marshall. "Especially since some of these pathways
contribute to the pathogenesis of autoimmune disease." For example, the team notes
that the single gene ACE has an impact on myocardial infarction, renal tubular dysgenesis,
Alzheimer's, the progression of SARS, diabetes mellitus, and sarcoidosis, yet recently ACE
has been shown to be affected by the common species Lactobacillus and Bifidobacteria.
Found in yogurt, these species are often considered to be innocuous or
"friendly." "No one would argue that these species aren't present in the
human body, yet there has been inadequate study of how these 'friendly' species affect
disease," states Amy Proal, the paper's lead author. "What we thought were
autoantibodies generated against the body itself can now be understood as antibodies
directed against the hidden bacteria," states Marshall. "In autoimmune disease,
the immune system is not attacking itself. It is protecting the body from pathogens."

APS-1 is an rare hereditary disease where the immune system attacks the body's own organs.
Within the framework of a major EU project, coordinated by Professor Olle Kšmpe at
Uppsala university, scientists have now managed to identify a protein that opens new
possibilities of understanding both APS-1 and other autoimmune disorders. The discovery is
being published in the American journal The New England Journal of Medicine.

Some researchers believe that Neolithic foods - the foods introduced into the human diet
at the start of the Neolithic Era - are the cause of autoimmune disease. Loren Cordain's
articles give details of the mechanism. The book NeanderThin is a case in point - written
by someone with multiple autoimmune disease who was healed by a paleolithic diet.

It's not just patients with autoimmune diseases like lupus and rheumatoid arthritis (RA)
that have self-attacking immune cellshealthy people have them too, according to a
new report in the Journal of Experimental Medicine. In healthy adults, however, these
cells are maintained in an 'off' state, perhaps explaining their innocuous nature. Whether
these cells are the true predecessors of the self-attacking cells prevalent in lupus and
RA and, if so, what prevents them from causing disease in everyone is not yet known. The
new study will appear online on December 22nd. As antibody-producing B cells develop in
the bone marrow, the body tests them to determine whether their antigen receptors are apt
to confuse self tissues for intruders. If so, their receptors are either rearranged to
make new, non-autoreactive versionsa process called 'receptor editing'or the
cells are killed off while still in the bone marrow. Yet a minority manages to escape,
slipping into the body as mature B cells with a propensity for self-attack.

Unexpected finding opens up new way
to stop autoimmune diseases and transplant rejection

After several years of battling recurring infections, the last thing a patient and her
doctors ever expected was that the cause of her problems might actually help millions live
longer, more active lives. Now, researchers have high hopes because Edward Goetzl and his
colleagues from the University of California and The Ohio State University discovered that
the patient made a unique antibody to her own T cells, the cells that mediate much of
autoimmunity. Acting on the surface of T cells via a novel mechanism, the antibody reduced
the number of T cells in her blood stream: a result that usually requires a host of
"immunosuppressive" and possibly toxic drugs. Their research discovery,
published online in The FASEB Journal, may lead to entirely new therapies for a wide range
of autoimmune disorders, such as colitis, lupus, rheumatoid arthritis, inflammatory bowel
disease, and multiple sclerosis, as well as new ways to prevent transplant
rejection."The possibility that these antibodies can be used to treat diverse
autoimmune diseases with minimal risk of infections represents a new horizon for reversing
these disabling and often fatal conditions," said Edward Goetzl, a senior researcher
involved in the study.

Scientists at UCSF have discovered an abnormality in a patients immune system that
may lead to safer therapies for autoimmune diseases such as rheumatoid arthritis and
colitis, as well as potential new ways to treat transplant rejection. The research
identified antibodies from a womans immune system that prevent infection-fighting T
cells from moving through her blood stream and entering her bodys organs to attack
invaders such as bacteria or viruses. Findings appear in the current online edition of
The FASEB Journal, the official journal of the Federation of American
Societies for Experimental Biology. Based on studies in which the womans antibodies
were transferred into mice, researchers hope these antibodies can be used to treat
patients with autoimmunity or transplant recipients whose immune systems attack a
transplanted organ or tissue. Autoimmunity occurs when the body perceives its own cells or
tissue as foreign organisms and creates an immune response to itself. Autoimmune diseases
affect approximately five to eight percent of Americans and their prevalence is
increasing, according to the National Institute of Allergy and Infectious Diseases. The
majority of people with autoimmune diseases are women.

Th1 inflammatory diseases are characterized by the generation of Interferon-gamma and with
it, 1,25-dihydroxyvitamin-D in response to intracellular bacteria. We are researching
which diseases show scientific evidence that they are due to a Th1 immune system
inflammatory response. There are hundreds of so-called 'autoimmune' diseases. Autoimmune
is a misnomer since the body's immune system is not attacking itself. We use this term
only because it is familiar and easily recognizable not because it is accurate. Many
common diseases like atherosclerosis are being recognised as having an inflammatory
component. We can make an educated guess about which diseases would be more difficult to
treat with the MP because the symptom exacerbation might be difficult to manage.

The Marshall Protocol is a curative treatment for diseases having a TH1 type immune
response. Patients having been diagnosed with one or more of a wide range of diseases have
been successfully treated using this protocol. It works by enabling the immune system to
destroy the intracellular bacteria that are thought to be the root cause of the illness.

CureMyTh1.org is moderated by folks with Th1 inflammatory disease who are being treated
with the Marshall Protocol (MP). They do not have medical expertise but are knowledgeable
about the disease process and the MP. They are eager to answer your basic questions so you
can decide if you would like to participate in the clinical study of the Marshall
Protocol.

Professor Trevor G. Marshall began studying chronic disease at the University of Western
Australia in 1978, with a focus on diabetes, infertility, and sarcoidosis. At the turn of
the 21st Century, he identified the pathogenesis of the Th1 immune system response 
an antibiotic-resistant, intra-phagocytic, metagenomic microbiota, consisting primarily of
pleomorphic, cell-wall-deficient (CWD) bacteria [1]. Tools of modern molecular genomics
enabled Dr. Marshall to develop an antibacterial protocol which stimulates innate immunity
at the same time as it weakens this metagenomic microbiota. The Phase II clinical trial
conducted by the Autoimmunity Research Foundation has demonstrated applicability of this
antibacterial therapy to a wide range of chronic Th1 immune illnesses [2]. This confirms
Dr. Marshalls prediction that most chronic disease springs from genomic variations
of the same fundamental mix of relatively common pathogens.

The Marshalls paper "Antibiotics in Sarcoidosis" [1] states that there are
many different species of Cell Wall Deficient (CWD) bacteria which can contribute to Th1
inflammation. It has become clear that low dose, pulsed Minocycline (Mino) used in Phase
One of the MP, while very effective, does not eliminate all the species of
intra-phagocytic bacteria needed to effect a cure. After exhaustive research, the
Marshalls have identified several other antibiotics which work by exerting a complimentary
blockade of bacterial-protein synthesis. When these antibiotics are taken along with Mino
(at low-dose, pulsed intervals), they are far more effective than if they were taken
alone. Benicar, taken 40mg every six hours both provides an inflammatory blockade and
re-activates the VDR Nuclear Receptor.

Scientists from the Scripps Research Institute and the Genomics Institute of the Novartis
Research Foundation have found a specific mutation that leads to the development of severe
autoimmune kidney disease in mice. The research sheds light on the basic biology of the
immune system, as well as on the effectiveness of drugs such as the anti-leukemia
medication Gleevec/Imatinib. The study was published in the January 16, 2009 edition
(Volume 33, No. 1) of the journal Molecular Cell. In the study, the scientists identify a
disease-causing mutation in a binding structure common to dozens of kinasesspecific
enzymes, especially important in cell signaling, that can modify other proteins by
transferring a phosphate group onto them. The mutation reduced the activity of an
important kinase, Lyn (a member of the Src family, which modulates important cellular
processes including cell migration, proliferation, and differentiation). "Our study
has several important implications," said Karsten Sauer, a Scripps Research scientist
and assistant professor who led the study. "First, it shows that when you eliminate
the activity of the Lyn kinase through mutation, you develop problems in B cell signaling,
resulting in B cell hyperactivity which leads to a severe autoimmune reactionin this
case, autoimmune glomerulonephritis, a form of kidney disease very similar to human lupus.
This shows for first time how essential the Lyn kinase activity, and not potential adaptor
or scaffold functions of the protein, is for B cell signaling, and for preventing
autoimmune disease." B cells produce pathogen-fighting antibodies and are a critical
part of the adaptive immune system.